The present case-control study evaluates the role of the progesterone receptor (PR) polymorphism known as PROGINS as a risk factor for ovarian cancer development and investigates the association between these genetic variants and clinical/pathologic variables of ovarian cancer. PROGINS polymorphism was examined, by polymerase chain reaction, in a total of 80 patients with ovarian cancer and 282 control subjects. The frequencies of PROGINS polymorphism T1/T1, T1/T2, and T2/T2 were 71.3, 15.0 and 13.8% in ovarian cancer patients and 78.37, 21.63 and 0% in controls, respectively. The chi(2)-test showed a higher incidence of the T2/T2 genotype (P=0.001) in the ovarian cancer group. In addition, women carrying a mutated allele (T2) showed approximately 2.2 times higher risk of ovarian cancer development as compared to women who have a variant allele (odds ratio (OR)=2.2; 95% CI=1.80-3.54). Regarding the clinical and pathologic findings observed within the cancer group, there was a significant correlation between PROGINS polymorphism and patients with a familial history (chi(2)=6.776; P=0.009; Fischer exact test, P=0.01). In this regard, patients with familial antecedents have a 4.7 times higher likelihood to have at least one risk allele (T2) as compared with patients without familial antecedents (OR=4.69; 95% CI=1.38-15.87). No correlations were observed among the other variables. These data suggest that the PROGINS polymorphism T2/T2 genotype might be associated with an increased risk of ovarian cancer.